title: Evaluation of analgesic, antioxidant, cytotoxic and metabolic effects of pregabalin for the use in neuropathic pain.
abstract: OBJECTIVE
  The aim of this research was to evaluate analgesic, antioxidant, metabolic, and cytotoxic effects of pregabalin (PGB), which is widely applied for the treatment of neuropathic pain syndromes in diabetic patients.
  
  
  METHODS
  We used the streptozotocin (STZ) model of painful diabetic neuropathy (PDN) in mice and we measured the effect of intraperitoneally administered PGB on tactile and thermal nociceptive thresholds in the von Frey and hot plate assays, respectively. The influence of PGB on the motor coordination of diabetic animals was investigated in the rotarod test. In vitro in HepG2 and 3T3-L1 cell lines cytotoxicity of PGB, its influence on glucose utilization, and lipid accumulation were assessed. The antioxidant capacity of PGB was evaluated spectrophotometrically using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method.
  
  
  RESULTS
  Pregabalin was a very efficacious antiallodynic and analgesic drug capable of increasing the pain thresholds for tactile allodynia and thermal hyperalgesia in diabetic mice. In the von Frey test at a dose of 30 mg/kg it elevated the pain threshold for 168% versus diabetic control and in the hot plate test this dose prolonged the latency time to pain reaction for 130% versus control value of diabetic mice. No motor deficits were observed in PGB-treated diabetic animals. In vitro PGB did not influence glucose utilization or lipid accumulation. No antioxidant or cytotoxic effects of PGB were observed at concentrations 1-100 μM.
  
  
  CONCLUSIONS
  Our experiments demonstrated significant antiallodynic and analgesic properties of PGB in mice. In vitro studies showed that this drug is metabolically neutral. It did not cause motor coordination impairments in diabetic animals either. These effects might be of great importance for diabetic patients.
authors.affiliation: Jagiellonian University, Cracow, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Sałat
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Librowski
authors.forename: Barbara
authors.initials: B
authors.lastname: Nawiesniak
authors.forename: Monika
authors.initials: M
authors.lastname: Gluch-Lutwin
mesh_terms: D041721:3T3-L1 Cells; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D009048:Motor Skills / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects; D000069583:Pregabalin; D000077154:Rosiglitazone; D016593:Terfenadine / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D000975:Antioxidants; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D016593:Terfenadine; D005947:Glucose